To assess the safety and feasibility of administering physiotherapy following psilocybin in patients with refractory motor Functional Neurological Disorder (FND), and to determine a treatment regimen that optimises symptom improvement.

FND is a common disorder, and existing treatments are often ineffective. There is a rationale that psychedelics may help modify abnormal beliefs regarding motor function in FND and augment physiotherapy to relieve symptoms. However, it is unclear if psychedelics are tolerated in this population and the optimal treatment regimen is unknown.

Single-site randomized pilot study comparing two treatment regimens in refractory motor FND: moderate dose (15mg) psilocybin with physiotherapy during the acute drug effects versus standard dose (25mg) psilocybin alone, followed by a 2-week physiotherapy course in both groups. Co-primary endpoints: safety, feasibility, Simplified Functional Motor Disorder Rating Scale (S-FMDRS) and Patient-reported Clinical Global Impression of Improvement (PGI-I) at 1-week / 1-month post-treatment.

24 subjects enrolled: 11 completed the moderate dose arm, 12 the high dose arm, 1 withdrew after baseline assessment. No major treatment-emergent adverse events. Mean change in S-FMDRS in the moderate (high) dose: -5.7 (-4.5) and -4.1 (-4.75) at 1 week and 1 month, respectively.  Mean PGI-I in the moderate (high) dose:  2.6 (2.5) and 2.2 (2.75) at 1 week and 1 month. Overall, 10 (90%) reported symptom improvement at both 1 week  / 1 month in the moderate dose arm, and 10 (83%) at both 1 week / 1 month in the high dose arm. 1 participant reported worsening at 1 week (both arms), and 1 at 1 month (high dose arm only).

This is the first study to combine psilocybin with physiotherapy in FND. The intervention was feasible, no major treatment-emergent adverse events were reported, and a signal of efficacy was observed in both arms. These findings will guide the design of a follow-up RCT.